POS0186 VOCLOSPORIN FOR LUPUS NEPHRITIS: RESULTS OF THE TWO-YEAR AURORA 2 CONTINUATION STUDY
Authors: A. Saxena, Y. K. O. Teng, C. Collins, N. England, H. Leher
Journal: Annals of the Rheumatic Diseases (2022)

Background Voclosporin (VCS), a novel calcineurin inhibitor, was approved in the US in January 2021 for the treatment of adult patients with active lupus nephritis (LN) in combination with background immunosuppressive therapy. The Phase 3 AURORA 1 study showed that the addition of VCS to mycophenolate mofetil (MMF) and low-dose steroids in patients with LN significantly increased rates of complete renal response at 52 weeks. Objectives Here we report the results of the completed continuation study, AURORA 2, which assessed the long-term safety and tolerability of VCS compared to placebo in patients with LN receiving treatment for an additional 24 months following completion of the AURORA 1 study Methods Key inclusion criteria for the parent AURORA 1 study included a diagnosis of biopsy-proven active LN (Class III, IV, or V ± III/IV), proteinuria ≥1.5 mg/mg (≥2 mg/mg for Class V) and estimated glomerular filtration rate (eGFR) &gt;45 mL/min/1.73 m 2 . Patients who completed AURORA 1 and who elected and were eligible to enter AURORA 2 continued on the same blinded therapy as at the end of AURORA 1 (either VCS or placebo twice daily in combination with MMF and low-dose steroids). Safety and tolerability were monitored, and eGFR, serum creatinine (SCr), and urine protein creatinine ratio (UPCR) were also assessed. Results In total, 116 and 100 patients in the VCS and control arms enrolled in AURORA 2, with 92 (79.3%) and 73 (73.0%) patients in each respective arm receiving treatment to the end of AURORA 2. There were no unexpected safety signals in the VCS arm compared to control, with similar rates of serious adverse events reported in both arms (VCS [18.1%] vs. control [23.0%]; Table 1). Eight patients in each arm experienced serious adverse events of infection; serious coronavirus infections were observed in 2 patients in the voclosporin arm and 5 patients in the control arm. There were 4 and 2 adverse events by preferred term of renal impairment reported in the VCS and control arms, respectively, none of which were considered serious, and no reports of acute kidney injury by preferred term in either arm. There were no deaths in the VCS arm during AURORA 2; four deaths were reported in the control arm (pulmonary embolism [n=1], coronavirus infection [n=3]). Mean eGFR and SCr levels remained stable through the end of AURORA 2. The difference between the VCS and control arms in LS mean change from baseline in eGFR was 2.7 mL/min/1.73 m 2 at 4 weeks following study drug discontinuation (Figure 1). The mean reductions in UPCR observed in patients treated with VCS in AURORA 1 were maintained in AURORA 2 with no increase in UPCR noted at the follow-up visit 4 weeks after study drug discontinuation. Table 1. Overall Summary of Adverse Events Control(n=100) Voclosporin(n=116) n (%) n (%) Any AE 80 (80.0) 100 (86.2) Renal Impairment 2 (2.0) 4 (3.4) Acute Kidney Injury 0 0 Treatment-related AE 21 (21.0) 28 (24.1) Serious AE 23 (23.0) 21 (18.1) Serious Treatment-related AE 2 (2.0) 1 (0.9) AE Leading to Study Drug Discontinuation 17 (17.0) 11 (9.5) Death 4 (4.0) 0 Treatment-related Death 0 0 Figure 1. LS Mean eGFR over Time Conclusion Voclosporin was well-tolerated over 3 years of treatment with no unexpected safety signals detected. Further, eGFR remained stable throughout the study period, and the significant and meaningful reductions in proteinuria achieved in AURORA 1 were maintained. These data provide evidence of a long-term treatment benefit of VCS in patients with LN. Includes adverse events starting on or after the first dose of study drug in AURORA 2 up to 30 days after the last dose and all events of death reported during study follow-up. Adverse events were aggregated by System Organ Class and Preferred Term and coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 20.0. AE, adverse event. Disclosure of Interests Amit Saxena Speakers bureau: Aurinia Pharmaceuticals Inc., Consultant of: Aurinia Pharmaceuticals Inc., Y.K. Onno Teng Consultant of: Aurinia Pharmaceuticals Inc., Chris Collins Shareholder of: Aurinia Pharmaceuticals, Employee of: Aurinia Pharmaceuticals, Nicole England Shareholder of: Aurinia Pharmaceuticals, Employee of: Aurinia Pharmaceuticals, Henry Leher Shareholder of: Aurinia Pharmaceuticals, Employee of: Aurinia Pharmaceuticals